Fentanyl or its citrate is a synthetic narcotic analgesic whose analgesic activity is about 100 times higher than that of morphine in the animal test.
Nowadays, the transdermally absorbable and sustained release preparation containing fentanyl for the therapy of cancer pain is commercialized and it retains almost the effective serum concentration for 24 to 72 hours after administration (see Japanese Patent Publication A 61-37725). However, in regard to said transdermally absorbable and sustained release preparation, as the absorption of the drug is mild after administration of it, and the effective serum concentration can not be obtained until 12 to 24 hours after initial administration, it is impossible to expect the quick analgesic effect. Furthermore, even after said transdermally absorbable and sustained release preparation is tore off from the skin, fentanyl remains in the corneum. Therefore, its absorption into body continues, the drug is hardly removed from the body, and the half-life of the serum concentration is long, 17 hours. As such, said transdermally absorbable and sustained release preparation is not suitable for the therapy for acute ache such as pang (breakthrough pain) which occurs while the preparation is continuously applied. Against such pang which occurs while said preparation being continuously applied, the immediately active morphine preparations (injections, oral preparations, suppositories) are additionally administered as a rescue-preparation (a preparation for emergently additional administration) in Japan.
In regard to a transdermally absorbable preparation containing fentanyl, other various preparations are proposed (see Japanese Patent Publication A 2000-44476, and Japanese Patent Publication A 10-45570).
On the other hand, the fentanyl preparation for mucous membrane of the oral cavity which is possible to quickly circulate through the whole body and is noninvasively administered (Trade name: Actiq) is sold in USA (see U.S. Pat. No. 4,671,953). This preparation is a candy-type preparation with a stick (lollipop). When pang occurs, the preparation is put between cheek and submaxillary gingivae and is sucked in a period of 15 minutes to absorb fentanyl citrate from mucous membrane of the oral cavity. The amount of the systemic transfer by absorption of the drug from mucous membrane of the oral cavity is about one fourth. The rest of it is swallowed with saliva and is gradually absorbed from a gastrointestinal tract. In regard to said preparation, the tip of the preparation with a stick must be put between cheek and submaxillary gingivae for 15 minutes to give much uncomfortable feeling in a mouth. However, when it is chewed, the swallowed amount becomes much and the amount absorbed from mucosal membrane of the oral cavity becomes less. When pang disappears, the drug becomes unnecessary and the administration of the drug is stopped. Even if the preparation is taken off from the oral cavity in such a case, the drug which was already transferred into a gastrointestinal tract continues to be absorbed thereafter. Therefore, it is difficult to control the serum concentration of the drug.
In addition, patches containing fentanyl for mucous membrane of the oral cavity are described in Japanese Patent Publication A 2002-275066, etc., but they are not yet put in practice.